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PubMed1972

The onset and development of transmission in the chick ciliary ganglion.

1. The onset and development of transmission has been studied electro-physiologically in the isolated chick ciliary ganglion from Stage 25 (Hamburger & Hamilton, 1951) until 28 days after hatching. Ultrastructure of the synapses was concomitantly investigated.2. Synaptic transmission began at Stage 26(1/2) and was 100% in both cell groups, ciliary and choroid, by Stage 33. It was initially chemical until Stage 41 when effective electrical coupling first appeared in the ciliary population. The proportion of electrically transmitting synapses increased to 80% by 1-2 days post-hatching.3. Few morphological synapses were present at Stage 33(1/2) when all ganglion cells were transmitting. A scarcity of synaptic vesicles persisted until late in embryonic development when all ciliary cells possessed calyces. At hatching the calyces were filled with synaptic vesicles.4. Initial synaptic contacts were by fine terminal branches often on the intricate processes of early ganglion cells. Calyces formed from Stage 36(1/2) and there was a concomitant retraction of ganglion cell processes, so that by Stage 40 all ciliary cells had simple calyces. The calyx was a transitory structure, which from the first week post-hatching began to break up into a cluster of boutons.5. Chemical post-synaptic potentials (PSPs) were at Stage 40 long (30 x the membrane time constant) and further prolonged by eserine. By Stage 43, PSPs had become markedly shortened and were unaffected by eserine. No simple explanation can be offered for the changes in PSP time course and sensitivity to anticholinesterases during development.6. Intracellular records from Stage 40 ciliary cells, which all possess calyces, showed 1-2 mV amplitude, diphasic, fast decaying electrical coupling potentials (CPs). Later in development the CPs became 20-40 mV amplitude, more slowly decaying and monophasic. This seemed to be correlated with faster presynaptic conduction velocities and myelination of the cell soma. Such changes in CPs may reflect a shift from capacitative to more resistive coupling and point to several factors contributing in varying degrees to the electrical transmission.7. Presynaptic fibres innervating ciliary cells were from the start of lower threshold and faster conduction velocity than those innervating ciliary cells, as occurred in the adult. It is concluded that these preganglionic fibres were probably specified by the time transmission starts and that they selectively innervated the proper post-synaptic cells.

Animals↗
PubMed2004

Extinct technetium in silicon carbide stardust grains: implications for stellar nucleosynthesis.

The isotopic composition of ruthenium (Ru) in individual presolar silicon carbide (SiC) stardust grains bears the signature of s-process nucleosynthesis in asymptotic giant branch stars, plus an anomaly in 99Ru that is explained by the in situ decay of technetium isotope 99Tc in the grains. This finding, coupled with the observation of Tc spectral lines in certain stars, shows that the majority of presolar SiC grains come from low-mass asymptotic giant branch stars, and that the amount of 99Tc produced in such stars is insufficient to have left a detectable 99Ru anomaly in early solar system materials.

Journal Article↗
PubMed1994

Anticipation resulting in elimination of the myotonic dystrophy gene: a follow up study of one extended family.

We have re-examined an extended myotonic dystrophy (DM) family, previously described in 1955, in order to study the long term effects of anticipation in DM and in particular the implications for families affected by this disease. This follow up study provides data on 35 gene carriers and 46 asymptomatic at risk family members in five generations. Clinical anticipation, defined as the cascade of mild, adult, childhood, or congenital disease in subsequent generations, appeared to be a relentless process, occurring in all affected branches of the family. The cascade was found to proceed asynchronously in the different branches, mainly because of an unequal number of generations with mild disease. The transition from the mild to the adult type was associated with transmission through a male parent. Stable transmission of the asymptomatic/mild phenotype showed a female transmission bias. We further examined the extent and causes of gene loss in this pedigree. Gene loss in the patient group was complete, owing to infertility of the male patients with adult onset disease and the fact that mentally retarded patients did not procreate. Out of the 46 at risk subjects in the two youngest generations, only one was found to have a full mutation. This is the only subject who may transmit the gene to the sixth generation. No protomutation carriers were found in the fourth and fifth generations. Therefore it is highly probable that the DM gene will be eliminated from this pedigree within one generation. The high population frequency of DM can at present not be explained by the contribution of asymptomatic cases in the younger generations of known families, but is probably caused by the events in the ancestral generations.

Adolescent↗
PubMed2003

Statistical process control as a tool for research and healthcare improvement.

Improvement of health care requires making changes in processes of care and service delivery. Although process performance is measured to determine if these changes are having the desired beneficial effects, this analysis is complicated by the existence of natural variation-that is, repeated measurements naturally yield different values and, even if nothing was done, a subsequent measurement might seem to indicate a better or worse performance. Traditional statistical analysis methods account for natural variation but require aggregation of measurements over time, which can delay decision making. Statistical process control (SPC) is a branch of statistics that combines rigorous time series analysis methods with graphical presentation of data, often yielding insights into the data more quickly and in a way more understandable to lay decision makers. SPC and its primary tool-the control chart-provide researchers and practitioners with a method of better understanding and communicating data from healthcare improvement efforts. This paper provides an overview of SPC and several practical examples of the healthcare applications of control charts.

Decision Making, Organizational↗
PubMed2001

Electrotonic structure of motoneurons in the spinal cord of the turtle: inferences for the mechanisms of bistability.

Understanding how voltage-regulated channels and synaptic membrane conductances contribute to response properties of neurons requires reliable knowledge of the electrotonic structure of dendritic trees. A novel method based on weak DC field stimulation and the classical method based on current injection were used to obtain two independent estimates of the electrotonic structure of motoneurons in an in vitro preparation of the turtle spinal cord. DC field stimulation was also used to ensure that the passive membrane properties near the resting membrane potential were homogeneous. In two cells, the difference in electrotonic lengths estimated with the two methods in the same cell was 6 and 9%. The majority of dendritic branches terminated at a distance of 1 electrotonic unit from the recording site. The longest branches reached 2 lambda. In the third cell, the difference was 36%, demonstrating the need to use both methods, field stimulation and current injection, for reliable measurements of the electrotonical structure. Models of the reconstructed cells endowed with voltage-dependent conductances were used to explore generation mechanisms for the experimentally observed hysteresis in input current-voltage relation of bistable motoneurons. The results of modeling suggest that only some dendrites need to possess L-type calcium current to explain the hysteresis observed experimentally and that dendritic branches with different electrotonical lengths can be bistable. Independent bistable behavior in individual dendritic branches can make motoneurons complex processing units.

Animals↗
PubMed1995

Using laser scanning confocal microscopy as a guide for electron microscopic study: a simple method for correlation of light and electron microscopy.

Anatomic study of synaptic connections in the nervous system is laborious and difficult, especially when neurons are large or have fine branches embedded among many other processes. Although electron microscopy provides a powerful tool for such study, the correlation of light microscopic appearance and electron microscopic detail is very time-consuming. We report here a simple method combining laser scanning confocal microscopy and electron microscopy for study of the synaptic relationships of the neurons in the antennal lobe, the first central neuropil in the olfactory pathway, of the moth Manduca sexta. Neurons were labeled intracellularly with neurobiotin or biocytin, two widely used stains. The tissue was then sectioned on a vibratome and processed with both streptavidin-nanogold (for electron microscopic study) and streptavidin-Cy3 (for confocal microscopic study) and embedded in epon/araldite. Interesting areas of the labeled neuron were imaged in the epon/araldite blocks with laser scanning confocal microscopy and then thin-sectioned at the indicated depth for electron microscopic study. This method provides an easy, reliable way to correlate three-dimensional light microscopic information with electron microscopic detail, and can be very useful in studies of synaptic connections.

Animals↗
PubMed1992

[The role of neuronal cytoskeleton associated proteins in neuronal network formation].

There have been many studies to determine extrinsic factors that may regulate the neuronal migration and growth of axons and dendrites. However, the intracellular mechanism, especially the regulation of cytoskeleton, has not been clarified. It has been reported that actin filament crosslinking protein, MAR-CKS, play roles in cell motility through cytoskeletal rearrangement accompanied by rapid, PKC-dependent phosphorylation. Recently, we have demonstrated that neuron-specific actin binding protein, drebrin, changed the stability and distribution of microfilaments within the fibroblast and formed highly-branched dendrite-like cell processes from their cell perimeters. It has also been reported that overexpression of microtubule associated protein, tau, in a fibroblast induced long axon-like cellular processes. This review will focus on dynamic regulations of the microfilament by drebrin and those of the microtubules by MAP2 and tau. Since all kinds of cytoskeletons are related to each other, the binding ability of neurofilament H to microtubules and that of MAP2 to neurofilaments were also discussed.

Actin Cytoskeleton↗
PubMed2000

Dissecting the Chemistry of Protein Splicing and Its Applications.

Protein splicing, the protein equivalent of RNA splicing, is a newly discovered posttranslational process that proceeds through a branched protein intermediate and produces two separate polypeptides from one gene. The experimental data used to distinguish among the proposed protein-splicing mechanisms are presented along with the progress made towards fully describing the mechanism. Numerous protein engineering applications using modified inteins have been developed, including the generation of alpha-thioesters in proteins, which circumvent the limits of solid-phase peptide synthesis.

Journal Article↗
PubMed1975

The fine structure of thymoma, with emphasis on its differential diagnosis. A study of ten cases.

In this study, thymoma is defined as a neoplasm of the epithelial-reticular framework cells of the thymus. As in the normal thymus, these cells regularly displayed branching tonofilaments, macuale adherens, elongated processes, and basal lamina. These characteristics proved useful in the differential diagnosis of thymoma from a variety of anterior mediastinal tumors including thymic carcinoid, lymphoma, germinoma (seminoma type), and fibrous mesothelioma. Lymphocytes in the thymomas often showed mitotic activity and a moderate degree of transformation. The significance of this and the gland-like spaces, vacuolated epithelial cells, starry-sky appearance, emperipolesis, and perivascular spaces is discussed.

Adolescent↗
PubMed1994

[Professionalization of physicians and health campaigns in twentieth-century Spain].

In this study we analyze the confluence of two processes that characterized the medical profession in Spain during the first third of the twentieth century. Health campaigns provided a formula for strengthening the interests of the professional collective by defining the demand for specific medical services, and consolidating the institutionalization of new areas of medicine, thus justifying their existence on a scientific basis. In addition, these health campaigns, to a great extent, based their propositions on the reputation of the specialist. We analyze two historical cases: the fight against infant mortality and the fight against cancer; the contributions of these two campaigns to the opening of a market for new specialist services, the role of technology, and processes of negotiation with other branches of medicine to guarantee a monopoly in providing treatment are examined.

Health Education↗
PubMed2003

[Roentgenosurgical treatment lesions of the brachiocephalic arteries].

Being the main cause of the lethality and permanent loss of work fitness, cerebrovascular diseases are assumed to be one of the most pressing problems of neurology and vascular surgery. It is to be noted that precisely stenotic and occlusive processes occurring in aortic arch branches induce ischemic lesions of the brain in half the cases. The multicenter cooperative randomized studies (MASCET, BCST, 'Veterans Affairs Cooperative Studies Program', VACT and ACAS) finalized the problem of the necessity of surgical treatment of patients with symptomatic and asymptomatic cerebrovascular insufficiency. However, despite the speedy progress in the cardiovascular surgery trend under consideration, a number of the fairly important problems remain unsolved. One of the important problems lies in the use of balloon angioplasty, stenting and thrombolysis of the precerebral arteries. The purpose of the study was to evaluate the results of roentrgenosurgical treatment of patients with hemodynamically significant lesion of the brachiocephalic arteries (BCA). Analysis was made of the treatment results in 19 patients aged 26 to 61 years. There were 13 (68.4%) men and 6 (31.6%) women. All the patients were provided different roentgenosurgical interventions on the BCA. Analysis of the results of roentgenosurgical interventions allowed to 7 establish that in the given patient group, the neurologic syinptomatology regressed, to an appreciable measure, with an improvement in the quality of life. It is noteworthy that roentgenosurgical interventions considerably shortened the patients' stay at hospital. The advantages of the technology are as follows: a possibility of the contact with the patient for the whole period of the procedure, minimization of the time of brain hypovolemia due to instrumental examinations. However, the risk of intraoperative complications requires a careful selection of the patients and impeccable technical performance.

Adult↗
PubMed2005

[The role of the extracellular space in biology of glial brain tumors].

The size, geometry and composition of the extracellular space (ECS) play an important role in influencing the biological behavior of primary brain tumors. Experiments employing the real-time TMA iontophoretic method to determine the size and geometry of the ECS, by monitoring the diffusion of TMA ions in the ECS, revealed a dramatic increase in ECS size in brain neoplasms when compared with that of unaffected brain cortex. Further, the increase of ECS volume in tumors was shown to correlate with increasing proliferative activity and increasing cellularity of astrocytomas. The increase in ECS size was surprisingly accompanied by a significant increase in diffusion barriers, slowing the diffusion of molecules in the ECS of tumors. In low-grade tumors, diffusion is hindered by the presence of a dense net of tumor cell processes. In high-grade gliomas, in which the cellular processes are shortened with reduced branching, the increase in diffusion barriers is caused by the overproduction of specific components of the extracellular matrix (ECM) by the tumor cells, mainly tenascin. The ECM glycoproteins produced represent a substrate for the subsequent adhesion and migration of tumor cells through the enlarged ECS. However, they might also critically reduce the diffusion of therapeutics into the tumor. The presence of tenascin in the ECS of a neoplasm correlates significantly with the increased malignancy of the tumor and a poor clinical outcome of the disease, thus making the immunohistochemical detection of tenascin diagnostically useful as a prognostic marker and a marker of aggressive biological behavior of tumors.

Brain Neoplasms↗
PubMed1991

Microvascular pericytes: a review of their morphological and functional characteristics.

A hundred years after the first description, many aspects of pericytes remain to be examined. Mesenchymal in origin, pericytes form an incomplete envelopment around the endothelial cells and within the microvascular basement membrane of capillaries and postcapillary venules. Morphologically, they appear as long, slender, polymorphic cells, showing an elongated cell body, from which arise longitudinal and circumferential branches. Cell bodies and cytoplasmic processes of pericytes, as well as the endothelial cells, are enveloped by the same basal lamina, except for where they make direct contacts with each other. The pericyte/endothelial cell contacts are peg and socket, adhesion plaques and gap junctions, making up structural mechanisms for force transmission and a possible receptor system for cells, in which the pericyte and endothelial cells respond to secondary signals generated in the other cells. Electron microscopic studies have revealed an elaborate network of cytoplasmic filaments. Pericyte intermediate filament proteins show species and tissue differences, expressing vimentin or vimentin and desmin. The pericytes also express protein typical of contractile cells, i.e. smooth muscle-specific isoforms of actin and myosin, cyclic GMP-protein kinase and tropomyosin. A gradual transition is observed between pericytes and smooth muscle cells in both terminal arterioles and venules. Several general functions for the pericytes have been postulated: contractability; permeability regulator; integrity maintainer; endothelial cell growth modulator; and cell progenitor with considerable mesenchymal potential.

Animals↗
PubMed1989

Preferential binding of radiolabeled poly-L-lysines to C6 and U87 MG glioblastomas compared with endothelial cells in vitro.

This report describes the preparation of polylysine-diethylene triamine pentaacetic acid (DTPA)-metal ion complexes and of iodinated polylysine derivatives and the preferential binding of these polymers to glioblastomas in culture. Synthetic polylysines (DP88 and DP299) were modified covalently either with the chelator DTPA or with 125I-Bolton Hunter reagent. The polylysine (DP88) was modified initially with fluorescein to permit fluorescence cytological studies and quantitative measurements of polylysine concentrations. The polylysines contained an average of one DTPA per 16 lysyl moieties. The polylysine-DTPA derivatives were then modified with a mixture of 153Gd and stable Gd. A copolymer (DP120) of lysine and tyrosine (4:1) was modified with 125I using chloramine T as catalyst. C6 (rat) and U87 MG (human) glioblastoma cells, in culture, bound six to seven times more polylysine-DTPA-Gd than endothelial cells from either aorta or brain. Each of the tumor cell types bound 10(8) molecules of the modified polylysine per cell when 2.5 x 10(5) cells were reacted with 50 micrograms or greater of the polylysine-DTPA-nuclide complex. The higher molecular weight polylysines delivered more radionuclide to the cells in culture. Although the tumor cells bound more [125I]polylysine and [125I]poly(lysine HBr,tyrosine) than they bound polylysyl-DTPA-Gd, the endothelial cells and the plastic culture dish also bound more of the iodinated polymers. The stoichiometry of polylysine bound per cell suggests that the sialic acid moieties on the cell surface are the primary binding sites for polylysine derivatives. Fluorescence microscopy studies revealed that the fluorescein polylysine (DP88) and the fluorescein polylysine-DTPA nuclide complex bound the tumor cells primarily at branch points along the neuritic processes, at the edge of the perikaryon and at the terminal regions of the outgrowth process. The polylysyl-DTPA-Gd can be used, with magnetic resonance imaging, to provide measurable contrast of the margin between C6 glioblastomas and normal brain in vivo in Wistar Furth rats.

Animals↗
PubMedDate not supplied

Evaluation of cerebrovascular processes and their reactions to pharmacotherapy by means of ultrasonic methods.

Calculation of diameter, wall movement, systolic and diastolic flow velocity in the vertebral and carotid artery by means of ultrasonic A-mode-echography and DOPPLER sonography permits identification and quantitative evaluation of cerebrovascular processes in extracranial and intracranial branches and their response to stress, especially in general and regionally accentuated arteriosclerosis, e.g. in predominant vertebrobasilar insufficiency. Their principal reagibility to pharmacotherapy under certain extracerebrovascular preconditions ins demonstrated by significant increase of the reduced hemodynamic parameters accompanied with significant elevation of decreased orthostatic BP after treatment with Raubasine, Dihydroergotamine and Dihydroergocristine.

Aged↗
PubMed1979

As it was in the beginning . . .the British Medical Association (Victorian Branch).

Branches of the British Medical Association arose throughout the Commonwealth, one of the later being in Victoria, one of the smaller and thickly populated of the States. There were the usual causes. Dissatisfaction led to cliques, views of ethics varied with age and position and ambitions clashed. But the immediate causa causans was the blackballing of a candidate whose merits were his own, but whose ancestory was condemned. His "fidus Achates", with many traits in common who had been 20 years the mainstay, and 18 years the Editor, of the existing and repellant Medical Society of Victoria, promptly resigned, and refused repeated offers to return even at the price of a testimonial. SoDr Neild and Dr Louis Henry came together and between them ran the Branch for years and in process of time took prominent positions medically, musically and many ways.

Australia↗
PubMed1979

[The fine structure of myotendinous and myo-epithelial junctions in the guinea pig tongue (author's transl)].

The insertion of muscle fibers in the subepithelial connective tissue layer of the guinea pig tongue was studied light and electron microscopically. Fibers of the tractus verticalis approach the epithelium penetrating the lamina propria, both the reticular and papillar layer. Terminating muscle fibers split up and form branching finger-like cytoplasmic processes. The myotendinous junctions of such terminal processes fine structurally correspond to myotendinous junctions generally observed in skeletal or smooth muscles. The entire brush-like formation, however, is more far-reaching and highly differentiated. Filament bundles (spine-like profiles) originate from the plasmalemma and extend to the lamina densa of the basal lamina, especially in those regions where actin filaments are attached to the plasmalemma. Microfibrils (10 to 12 nm diameter) reach the lamina densa of the basal lamina. They form bundles which are continuous with fibrotubular strands of elaunin fibers and elastic fiber microfibrils. Furthermore, microfibrils are interwoven with collagen fibrils.

Animals↗
PubMed1995

[The concept of the pathogenesis of occlusive disorders in diseases of the temporomandibular joint].

Abnormal occlusion developing in adult patients is always caused by involvement of the temporomandibular joints. Destructive diseases of an infectious origin are characterized by unilateral involvement of the joints, unilateral reduction of the interocclusal height, and increased abrasion of teeth due to increased masticatory loading. Occlusive contact is preserved in all teeth. The second group of destructive diseases of the temporomandibular joint includes rheumatoid arthritis and systemic scleroderma and is characterized by symmetrical involvement, polyarthritis, and rapid progress. Clinically frontal occlusion develops, which is caused by deformation of articular processes, mandibular body, angle, and branch.

Adolescent↗